Synaptic Physiology I-III

Question 1

Action potential mechanism

Answer 1

• Na⁺ channel gate is triggered to open via stretch/other stimulus
• Na⁺ flows in ==> membrane depolarization
• Voltage-gated Na⁺ channels open ==> increased Na⁺ flow inwards
  
  • Action potential will occur completely if membrane reaches threshold potential
• Inactivation gates begin to close on voltage-gated Na⁺ channels ==> slowing of Na⁺ flow
• K⁺ channels open ==> K⁺ flows out of cell ==> cell repolarizes
• Ion channels reset to resting position & Na/K transporter helps restore resting membrane potential

Question 2

Electric synaptic transmission definition/characteristics

Answer 2

• Gap junctions allow direct passage of electrical signal between cells
• Rare in nervous system of mammals
  
  • Chemical synaptic transmission dominates the nervous system
• Important in fxning of heart, smooth muscle, embryonic cells, and epithelia

Question 3

Major limitation of electrical vs. chemical synaptic transmission

Answer 3

• presynaptic terminal must be comparable in size to postsynaptic cell in order to provide enough current to depolarize the cell
  
  • would not fxn @ a neuromuscular jxn b/c the current generated by the much smaller neuron would not generate enough depolarization @ muscle
• electric transmission is by default excitatory ==> more difficult to integrate excitatory and inhibitory synpatic inputs as is achieved at chemical synapses

Question 4

Mechanism of NT release at the presynaptic cell

Answer 4

• AP reaches the end of the cell (“active zone”)
  
  • Active zone E_Ca = +120mV b/c the concentration of Ca²⁺ is significantly higher outside the cell
• Ca²⁺ channels open ==> Ca²⁺ flows in quickly
• Ca²⁺ attaches to vesicles containing NTs via SNARE proteins ==> fusion of vesicle to cell
• NTs escape into the synaptic cleft

Question 5

SNARE proteins involved in NT release

Answer 5

• Located on NT vesicles:
  
  • Synaptotagmin
  • Synaptobrevin
• Located on surface membrane:
  
  • Syntaxin
  • SNAP-25

Question 6

Mechanism of SNARE-mediated vesicle fusion

Answer 6

• Ca²⁺ attaches to synaptotagmin (located on vesicle)
• Synaptobrevin, syntaxin, and SNAP-25 form a super-helix used to fuse with the membrane
• Vesicle fuses with membrane and NTs are released into the synaptic cleft

Question 7

Presynaptic events involved in cleanup/recycling (occuring outside the cells)

Answer 7

• reuptake: pumps bring NTs back into the cell for reuse
• degradation: e.g. AChE ==> acetate + choline
• diffusion into ECF

Question 8

Presynaptic events involved in cleanup/recycling (occuring inside the cells)

Answer 8

• Na/K pump: restores sodium/potassium ion balance
• ATP & NCX pumps: calcium exchanger helps restore calcium ion balance
• Endocytosis of vesicles
  
  • clathrin + clathrin adapter induce the reformation of vesicles
  • dynamin (“pinch-ase”) separates the vesicle from the membrane
  • vesicle loses its coating and is refilled with NTs

Question 9

Major function of motor nerve terminal

Answer 9

• AP from CNS ==> enough ACh to depolarize muscle fiber to threshold for AP
• Muscle fiber resting = -80mV & threshold = -50mV ==> enough ACh to depolarize muscle by at least 30mV

Question 10

Mechanism of signal amplification @ NMJ

Answer 10

• Synaptic vesicle contains thousands of ACh mlx ==> ~half consumed by AChE + 2ACh/receptor ==> activation of >1000 postsynaptic ACh receptors
  
  • each receptor ==> 1000nV of positive charge = 1microV
  • 1000 x 1microvolt = ~1mV/vesicle
• Need @ least ~30 vesicles to reach threshold
• 1 AP ==> 100 quanta (vesicles) in order to maintain sustained muscle use
• Amplification accomplished by releasing a large amount of NTs for each AP

Question 11

Facilitation & Depression of NT release (definition)

Answer 11

• During repetitive nerve stimulation…
• facilitation = calcium ion concetration builds up
• depression = pool of releasable vesicles is depleted

Question 12

Mechanism of facilitation of NT release

Answer 12

• Ca²⁺ concentration @ terminal rises during h_igh frequency stimulation_ b/c there is not enough time to restore Ca²⁺ balance
• Exocytosis depends on Ca²⁺, therefore number of quanta released will increase due to residual Ca²⁺

Question 13

Mechanism of depression of NT release

Answer 13

• repetitive stimulation ==> nerve terminal runs out releasable vesicles
  
  • terminal cannot replenish synaptic vesicles from reserve pool fast enough to meet demand
• Exocytosis depends on supply of synaptic vesicles, therefore number of quanta released will decrease

Question 14

Myasthenic syndrome characteristics

Answer 14

• Ab againsts Ca²⁺ channels
• Characteristically weak, but can fire APs @ muscle & improve strength with effort
  
  • relies on facilitation to build up enough Ca²⁺ to release enough NTs to generate APs @ muscle

Question 15

Myasthenia gravis characteristics

Answer 15

• Disease w/Abs against AChR ==> initial strength is good, but tire very quickly
  
  • With fewer postsynaptic AChR, M.G. people generally need to release more quanta to fire APs
  • Due to synaptic depression (reduction of 10% of available quanta/AP), M.G. people quickly fall below the required number of quanta to fire APs @ muscle

Question 16

Mechanism of fast vs. slow synapses (e.g. of physiologic responses)

Answer 16

• determined by type of receptor on the postsynaptic cell
• fast = direct = ligand/ion-gated channel
  
  • e.g. muscle contraction
• slow = indirect = g-protein-coupled receptors
  
  • e.g. emotion

Question 17

Characteristics of fast channels

Answer 17

• selective = allows a single type of ion
  
  • Na⁺ selective = excitatory
  • K⁺ selective = inhibitory
• non-selective = allows both Na⁺ and K⁺ to flow across
  
  • fastest-acting channel
  • ending membrane potential will rise above level needed to depolarize

Question 18

Characteristics of slow channels

Answer 18

• Slow receptors act indirectly ==> no channel is opening upon binding to receptor
• Slow receptors couple w/g-proteins and/or 2nd messenger systems
• NT binds to receptor ==> activation of g-protein/2nd messenger ==> reaction w/in cell:
  
  • e.g. opening of a separate channel (temporary)
  • e.g. effector entering nucleus to alter gene transcription (permanent/semi-permanent)

Question 19

Electrical “driving force” definition

Answer 19

• difference between membrane potential and equilibrium potential of a particular ion ==> induces flow across the membrane if physically permitted

Question 20

Characteristics of synaptic reversal potential

Answer 20

• NSC (Non-selective cation) channel is permeable to both Na⁺ and K⁺ ==> brings membrane potential to value midway between E_Na & E_K ==> “synaptic reversal potential”
  
  • AChR @ NMJs operate in this way
• Reversal potential for NSC channels = -10mV which >-55mV ==> these channels are excitatory

Question 21

Channels involved during fast inhibition @ CNS

Answer 21

• GABA binding induces opening of Cl^- channels

Question 22

Mechanism of amplified strength of individual IPSP

Answer 22

• **Membrane potential is determined by relative permeabilities of all participating ions
• IPSP @ 1mV ==> huge permeability change if ion’s equilibrium potential is near resting potential ==> E_Cl ~ E₀

Question 23

Spatial and temporal summation of postsynaptic potentials (definition)

Answer 23

• spatial summation = two or more different inputs contribute
  
  • e.g. various excitatory inputs coverge on a motor neuron fire simultaneously ==> combine (“summate”) to drive membrane potential to threshold for AP
• temporal summation = same input is stimulated multiple times in succession

Question 24

Mechanisms for removing NTs from synaptic clefts

Answer 24

• reuptake: pumps bring NTs back into the cell for reuse
• degradation: e.g. AChE ==> acetate + choline
• diffusion into ECF

Question 25

Generic types of dendritic receptors

Answer 25

• NMDA receptors
• AMPA receptors

Question 26

Coincidence detector characteristics

Answer 26

• Major criteria for coincidence detector:
  
  • can detect the presence of NT in cleft
  • can detect change in membrane potential
• Coincidence detectors = key for associative learning
  
  • “make synapses smart”
• e.g.: NMDA receptor

Question 27

Calcium impact on postsynaptic dendrites @ CNS

Answer 27

• Calcium induces vesicles w/AMPA receptors to fuse with membrane
• Increased AMPA receptors @ surface ==> next synapse firing = larger postsynaptic response

Question 28

Mechanism of coincidence detector via NMDA receptor

Answer 28

• NMDA opens in presence of presynaptic NTs + APs generated at a different dendrite/location in the neuron
  
  • NMDA pore is plugged by Mg2+ @ rest
  • NMDA channel gate is opened by the presence of glutamate (NT presence)
  • Mg2+ is repelled in presence of positive charge (firing of AP), allowing Ca2+ to enter cell
• ​If an AP occurs + NT release at the presynaptic neuron ==> open NMDA channels ==> Ca²⁺ influx ==> increased AMPA channels ==> stronger connection w/presynaptic neuron